Observation of industrial hygiene has substantially improved working environments in the recent past. Nevertheless, accidental and unavoidable exposures occur and the need to assess these exposures remains.
Physiologically based pharmacokinetic (PBPK) models are frequently used to describe the biokinetics of a chemical in experimental animals, and can be used to predict human tissue levels of a hazardous chemical following exposure. The process of developing a PBPK model typically includes validation studies to experimentally test model assumptions and hypotheses. A validation study generally involves monitoring a biomarker, or a change in the biological system that can be related to an exposure or effect from a toxic agent. Common biomarkers include the presence of the parent compound and/or metabolites in blood, in exhaled breath, or in excreted urine or feces.
Analysis of exhaled breath represents a non-invasive method for detecting exposure to a particular toxicant. Breath measurements are useful in environmental exposure studies, and may provide evidence about previous long-term or repeated exposures in environments that are not easy to monitor (Bond et al. 1992). If breath samples are collected during, or immediately following, a short-term exposure, breath measurements can be used to predict the peak exposure. Previous breath-sampling methodologies have been to collect repeated 1-min breath samples at 5-min intervals (Raymer et al. 1990). Although this method can aid in describing the rapid exponential emptying of the blood compartment that occurs immediately following peak exposure, sampling in 5-min intervals still forces an approximation of the true shape of the clearance kinetics. This is because people breath at a rate of about 20 breaths per minute.
Presently, personnel wear an external exposure dosimeter commonly known as a lapel chemical sampler (lapel pin) that is a small glass or metal hollow vial or tube in the shape of a cylinder, the tube having a chemical sorbent coated on the internal wall surface. As air passes through the tube, any chemical compatible with the sorbent is sorbed thereon for quantification by later desorbtion and chemical analysis, for example by a gas chromatograph mass spectrometer. In addition, personnel exhale into a plastic bag that is sealed, then later quantified by chemical analysis in a mass spectrometer. The identified chemicals and concentrations of each chemical may be entered into a physiologically based pharmacokinetic (PBPK) algorithm programmed on a computer. The result or output of the computer analysis is an estimate of internal tissue dose.
Presently, the external exposure dosimeter or lapel pin and breath samples are sent to a central laboratory for chemical analyses and subsequent quantitative analyses. These analyses require about 4-8 weeks on a routine basis and if there is a known emergency, require about 24 hours. This time lag between exposure and analysis is significant for at least three reasons. First, if an exposure requires treatment, the treatment is delayed by the amount of time for analysis, and second, the analysis uncertainty is greater with increased time between actual exposure and chemical analysis of that exposure. Thirdly, the use of the separate single-point measurements of breath and external dosimeter is inadequate for quantitatively assessing the total integrated exposure, dose, and predicted response of a worker exposed to hazardous chemicals. Previously reported batch collection methods (Thomas et al. 1991), such as collection of samples on sorbents or in canisters, integrate or average the concentration data over the collection or sampling period and may miss vital trend data.
Hence, there is a need for a method and apparatus that would provide real time chemical and quantitative analyses of internal tissue dose.